An examination of fungi sourced from peat bogs has discovered multiple species that generate substances harmful to the bacterium responsible for tuberculosis in humans. These results indicate that a viable approach for creating improved treatments may involve focusing on biological functions within the bacterium that regulate the levels of thiols.
An examination of fungi sourced from peat bogs has discovered multiple species that generate substances harmful to the bacterium responsible for tuberculosis in humans. These results indicate that a viable approach for creating improved treatments may involve focusing on biological functions within the bacterium that regulate the levels of thiols. Neha Malhotra from the National Institutes of Health in the U.S. and her team shared these findings on December 3 in the open-access journal PLOS Biology.
Each year, millions suffer from tuberculosis, leading to over a million deaths globally, even though the disease is treatable and preventable. The prolonged regimen of daily antibiotics lasting several months can be quite challenging, highlighting the urgent need for new treatments that reduce the duration of therapy.
To investigate potential targets for shortening treatment durations, Malhotra and her team examined sphagnum peat bogs. These freshwater wetlands are home to a wide variety of bacteria from the Mycobacterium genus, which includes the bacterium Mycobacterium tuberculosis that causes tuberculosis. In these bogs, fungi compete with mycobacteria to thrive in a decomposing “gray layer,” characterized by being acidic, low in nutrients, and lacking oxygen, much like the lesions observed in tuberculosis patients’ lungs.
In their laboratory, the researchers cultured Mycobacterium tuberculosis alongside approximately 1,500 different species of fungi gathered from the gray layer of several northeastern U.S. peat bogs. They discovered five fungi with toxic effects on the bacterium. Subsequent experiments in the lab focused on three specific substances produced by these fungi: patulin, citrinin, and nidulalin A.
These three compounds disrupt the tuberculosis bacterium by significantly altering the levels of thiols, which are essential for important molecular processes that keep bacterial cells viable and functioning.
While the researchers conclude that these compounds may not be ideal candidates for drug development, they suggest that their research supports a strategic approach for creating drugs that can shorten treatment duration by targeting the biological mechanisms that control thiol levels in the tuberculosis bacterium.
They remark, “Pathogenic mycobacteria, including those responsible for leprosy and tuberculosis, thrive in sphagnum peat bogs, where the acidic, low-oxygen, and nutrient-poor conditions foster intense microbial competition. By isolating fungi from these environments and testing their interaction with mycobacteria, we found that these fungi all influence the same physiological processes in mycobacteria but employ different chemical methods.”
